Sökning: WFRF:(Olerud Johan)
> (2005-2009) >
Improved vascular e...
Improved vascular engraftment and graft function after inhibition of the angiostatic factor thrombospondin-1 in mouse pancreatic islets
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- Olerud, Johan (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Per-Ola Carlsson
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- Johansson, Magnus (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Per-Ola Carlsson
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- Lawler, Jack (författare)
- Harvard University
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- Welsh, Nils (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Carlsson, Per-Ola (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Institutionen för medicinska vetenskaper,Per-Ola Carlsson
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(creator_code:org_t)
- American Diabetes Association, 2008
- 2008
- Engelska.
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 57:7, s. 1870-1877
- Relaterad länk:
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http://diabetes.diab...
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https://urn.kb.se/re...
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https://doi.org/10.2...
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Abstract
Ämnesord
Stäng
- OBJECTIVE: Insufficient development of a new intra-islet capillary network after transplantation may be one contributing factor to the failure of islet grafts in clinical transplantation. The present study tested the hypothesis that the angiostatic factor thrombospondin-1 (TSP-1), which is normally present in islets, restricts intra-islet vascular expansion posttransplantation. RESEARCH DESIGN AND METHODS: Pancreatic islets of TSP-1-deficient (TSP-1(-/-)) mice or wild-type islets transfected with siRNA for TSP-1 were transplanted beneath the renal capsule of syngeneic or immunocompromised recipient mice. RESULTS: Both genetically TSP-1(-/-) islets and TSP-1 siRNA-transfected islet cells demonstrated an increased vascular density when compared with control islets 1 month after transplantation. This was also reflected in a markedly increased blood perfusion and oxygenation of the grafts. The functional importance of the improved vascular engraftment was analyzed by comparing glucose-stimulated insulin release from islet cells transfected with either TSP-1 siRNA or scramble siRNA before implantation. These experiments showed that the increased revascularization of grafts composed of TSP-1 siRNA-transfected islet cells correlated to increments in both their first and second phase of glucose-stimulated insulin secretion. CONCLUSIONS: Our findings demonstrate that inhibition of TSP-1 in islets intended for transplantation may be a feasible strategy to improve islet graft revascularization and function.
Nyckelord
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Diabetes
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